The proposed research is designed to assess the relationship between the detailed molecular structure of a phospholipid bilayer as a function of: a) its ability to bind prothrombin; and b) enhance the rate of conversion of prothrombin to thrombin by Factor Xa in the presence of an optimal concentration of calcium ions, in vitro (functional definition of thrombogenicity). As a working hypothesis, it is proposed that the combined effects of prothrombin and Ca2 ion may induce in fluid lipid bilayers the particular lipid rearrangements (lateral domain formation) necessary to promote the binding of prothrombin to the membrane, resulting in its subsequent activation. In order to test this hypothesis, the following approaches will be used: 1) chemical synthesis of phospholipids of known structure; 2) physical studies on the properties of the unilamellar structures (bilayer vesicles) formed by these phospholipid in aqueous media; 3) characterization of the interactions of the lipid binding polypeptide of prothrombin (fragment 1) with these lipid surfaces as a model system, in vitro; and 4) characterization of those phospholipid surface properties that enhance phospholipid thrombogenicity. The utilization of highly characterized, synthetic phospholipids and purified clotting factors will permit analysis of their specific contribution. The long-term goal of this research is the continued development of a practical model system on which further studies of protein-lipid interactions in blood coagulation may continue, particularly the participation of platelet membranes in the formation of the prothrombin-and the FX-converting enzyme complexes.